DESCRIPTION: Exposure to extremely low frequency (ELF) fields has been shown to have a number of significant effects upon biological systems and concern has been raised about possible health hazards associated with that exposure. The full spectrum of biological activities of ELF fields is not known, and varying claims have been made regarding oncogenic potential on the one hand, and potential therapeutic benefits on the other. The studies planned in this proposal will examine the hypothesis that exposure to 60 Hz magnetic fields of varying amplitude and exposure duration may produce changes in the relationship of cellular proliferation and differentiation in an in vivo developmental model of endochondral ossification. This model exhibits developmental sequences of proliferation and differentiation and, since it has been well characterized in morphological, biochemical and molecular terms, it serves as an excellent test system to examine the effects of ELF field exposure upon the genomic regulation of proliferation and differentiation. The mode is applicable to issues of cell regulation in general and has important cellular analogies to skeletal embryogenesis and teratology, growth and repair and, by extrapolation, to oncogenesis. The observations of Stein and Lian indicate that a proliferation- differentiation relationship exists in experimental endochondral ossification and that this relationship can be modified by hormonal and other influences such that differentiation can be accelerated or retarded with reciprocal effects on proliferation. The observations of Aaron and Ciombor, with the same system of experimental endochondral ossification, indicate that the elaboration of extracellular matrix proteoglycan and the expression of mRNA for proteoglycan core protein can be accelerated by exposure to ELF fields and that this stimulation resides in the progenitor cell pool. These two sets of observations form the basis for the experimental approach for this proposal. Their experimental approach will measure expression of pertinent genes and will assess whether ELF fields can act as a signaling mechanism and alter the genomic regulation of proliferation and differentiation. These results will lend insight into ELF field effects upon fundamental regulatory processes with broad biological applicability.